scholarly journals Mechanisms of Photoreceptor Death in Retinitis Pigmentosa

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1120
Author(s):  
Fay Newton ◽  
Roly Megaw
Keyword(s):  
Retinitis Pigmentosa ◽  
Apoptotic Cell ◽  
Gene Replacement ◽  
Innate Immune ◽  
Cone Photoreceptor ◽  
Cell Death Pathways ◽  
Retinal Photoreceptors ◽  
Photoreceptor Death ◽  
Made In

Retinitis pigmentosa (RP) is the most common cause of inherited blindness and is characterised by the progressive loss of retinal photoreceptors. However, RP is a highly heterogeneous disease and, while much progress has been made in developing gene replacement and gene editing treatments for RP, it is also necessary to develop treatments that are applicable to all causative mutations. Further understanding of the mechanisms leading to photoreceptor death is essential for the development of these treatments. Recent work has therefore focused on the role of apoptotic and non-apoptotic cell death pathways in RP and the various mechanisms that trigger these pathways in degenerating photoreceptors. In particular, several recent studies have begun to elucidate the role of microglia and innate immune response in the progression of RP. Here, we discuss some of the recent progress in understanding mechanisms of rod and cone photoreceptor death in RP and summarise recent clinical trials targeting these pathways.

Arsenic Trioxide-Induced Cell Death Occurs Partially Independent of the Pro-Apoptotic Bcl-2-Family Members Bax and Bak.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4585-4585
Author(s):  
Christian Scholz ◽  
Antje Richter ◽  
Anja Richter ◽  
Bernd Dörken ◽  
Peter T. Daniel
Keyword(s):  
Cell Death ◽  
Arsenic Trioxide ◽  
Cell Lines ◽  
Apoptotic Cell ◽  
Family Members ◽  
Death Receptor ◽  
Hematologic Malignancies ◽  
Mitochondrial Pathway ◽  
Cell Death Pathways

Abstract Arsenic trioxide (As2O3, arsenite) efficiently kills cells from various hematologic malignancies and has successfully been employed for the treatment of acute promyelocytic leukaemia, myelodysplastic syndrome, and multiple myeloma. Investigating the mechanisms of arsenic trioxide-induced cell death, we recently demonstrated that arsenite-mediated cell demise has a partially necrotic phenotype, occurs independently of the extrinsic death receptor pathway of apoptosis, and is not hampered by the absence of functioning caspases. On the contrary, cell death proceeded entirely via an intrinsic, mitochondrial pathway and was efficiently blocked by the anti-apoptotic Bcl-2 family members Bcl-2 or Bcl-xL. Here, we address the role of the pro-apoptotic multi-domain Bcl-2 family members Bax and Bak. By employing different cell lines deficient for Bax and/or Bak, we demonstrate that Bax- or Bak-deficiency as well as the combined absence only partially blocks arsenite-induced cell death. While the detection of an additive effect of the combined Bax-/Bak-deficiency argues for a non redundant function of Bax and Bak, the persistence of a substantial percentage of arsenite-mediated cell demise in different double deficient cell lines nevertheless suggests a mode of arsenic trioxide-mediated cell death independent from these central inducers of apoptotic cell demise. The presented data add to the notion that arsenic trioxide kills tumor cells independent of the apoptotic machinery, and warrants further investigation on the efficacy of this compound in malignancies with deficiencies of the apoptotic cell death pathways.

scholarly journals A Brief Review on the Pathological Role of Decreased Blood Flow Affected in Retinitis Pigmentosa

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yi Jing Yang ◽  
Jun Peng ◽  
Deng Ying ◽  
Qing Hua Peng
Keyword(s):  
Blood Flow ◽  
Chinese Medicine ◽  
Retinitis Pigmentosa ◽  
Blood Stasis ◽  
Modern Medicine ◽  
Specific Mechanism ◽  
Chinese Herbal ◽  
Positive Effect ◽  
Made In

Retinitis pigmentosa (RP) represents a clinically and genetically heterogeneous disease characterized by progressive photoreceptor loss. In recent years, research has been rarely made in blood flow affected in RP. The specific mechanism of blood flow affected in RP is not completely clear. A number of studies indicated that the decreased blood flow was related to RP. According to clinical observation and treatment experience, Chinese medicine considered that blood stasis runs throughout the RP disease progression, and the blood stasis corresponding to Chinese herbal medicine has a positive effect on the clinical treatment of RP. Therefore, we proposed that the decreased blood flow may participate in the lesion. In this article, we will review the findings on the decreased blood flow affected in RP from the perspective of modern medicine and Chinese medicine.

scholarly journals Long-term rescue of cone photoreceptor degeneration in retinitis pigmentosa 2 (RP2)-knockout mice by gene replacement therapy

2015 ◽  
Vol 24 (22) ◽  
pp. 6446-6458 ◽  
Author(s):  
Suddhasil Mookherjee ◽  
Suja Hiriyanna ◽  
Kayleigh Kaneshiro ◽  
Linjing Li ◽  
Yichao Li ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Replacement Therapy ◽  
Knockout Mice ◽  
Gene Replacement ◽  
Cone Photoreceptor ◽  
Photoreceptor Degeneration ◽  
Gene Replacement Therapy

scholarly journals Recent advances in understanding and managing asthma

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2052 ◽  
Author(s):  
Su-Ling Loo ◽  
Peter A.B. Wark
Keyword(s):  
Immune Responses ◽  
Severe Asthma ◽  
Childhood Asthma ◽  
Airway Epithelium ◽  
Innate Immune ◽  
Type Ii ◽  
Asthma Treatment ◽  
Acquired Immune Responses ◽  
Made In

This review highlights the important articles published in the area of asthma research from January 2015 to July 2016. In basic science, significant advances have been made in understanding the link between the innate immune response and type II acquired immune responses in asthma and the role of the airway epithelium. Novel information continues to emerge with regard to the pathogenesis and heterogeneity of severe asthma. There have been important translational clinical trials in the areas of childhood asthma, treatment of allergy to improve asthma outcomes, and improving drug delivery to optimize the management of asthma. In addition, there are increasing data concerning the application of biological agents to the management of severe asthma. This body of work discusses the most notable advances in the understanding and management of asthma.

Photoreceptor actin dysregulation in syndromic and non-syndromic retinitis pigmentosa

2018 ◽  
Vol 46 (6) ◽  
pp. 1463-1473 ◽  
Author(s):  
Roly Megaw ◽  
Toby W. Hurd
Keyword(s):  
Retinitis Pigmentosa ◽  
Sensory Neurons ◽  
Intimate Relationship ◽  
Progressive Loss ◽  
Retinal Photoreceptors ◽  
Cilia Formation ◽  
Causal Genes ◽  
Dynamic Morphology ◽  
Cytoskeletal Elements

Retinitis pigmentosa (RP) is the leading cause of inherited blindness. RP is a genetically heterogeneous disorder, with more than 100 different causal genes identified in patients. Central to disease pathogenesis is the progressive loss of retinal photoreceptors. Photoreceptors are specialised sensory neurons that exhibit a complex and highly dynamic morphology. The highly polarised and elaborated architecture of photoreceptors requires precise regulation of numerous cytoskeletal elements. In recent years, significant work has been placed on investigating the role of microtubules (specifically, the acetylated microtubular axoneme of the photoreceptor connecting cilium) and their role in normal photoreceptor function. This has been driven by the emerging field of ciliopathies, human diseases arising from mutations in genes required for cilia formation or function, of which RP is a frequently reported phenotype. Recent studies have highlighted an intimate relationship between cilia and the actin cystoskeleton. This review will focus on the role of actin in photoreceptors, examining the connection between actin dysregulation in RP.

scholarly journals The Role of Interleukin-1β in Destruction of Transplanted Islets

2020 ◽  
Vol 29 ◽  
pp. 096368972093441
Author(s):  
Cheng Chen ◽  
Pengfei Rong ◽  
Min Yang ◽  
Xiaoqian Ma ◽  
Zhichao Feng ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Graft Loss ◽  
Innate Immune ◽  
Interleukin 1Β ◽  
Cell Replacement Therapy ◽  
Tremendous Progress ◽  
Made In

Islet transplantation is a promising β-cell replacement therapy for type 1 diabetes, which can reduce glucose lability and hypoglycemic episodes compared with standard insulin therapy. Despite the tremendous progress made in this field, challenges remain in terms of long-term successful transplant outcomes. The insulin independence rate remains low after islet transplantation from one donor pancreas. It has been reported that the islet-related inflammatory response is the main cause of early islet damage and graft loss after transplantation. The production of interleukin-1β (IL-1β) has considered to be one of the primary harmful inflammatory events during pancreatic procurement, islet isolation, and islet transplantation. Evidence suggests that the innate immune response is upregulated through the activity of Toll-like receptors and The NACHT Domain-Leucine-Rich Repeat and PYD-containing Protein 3 inflammasome, which are the starting points for a series of signaling events that drive excessive IL-1β production in islet transplantation. In this review, we show recent contributions to the advancement of knowledge of IL-1β in islet transplantation and discuss several strategies targeting IL-1β for improving islet engraftment.

ASPECTS IN BUILDING A COMPANY WEB-SITE AND ITS ROLE FOR THE DEVELOPMENT OF BUSINESS

2018 ◽  
pp. 117-124
Author(s):  
Petar Halachev ◽  
Victoria Radeva ◽  
Albena Nikiforova ◽  
Miglena Veneva
Keyword(s):  
Life Cycle ◽  
Web Site ◽  
The Internet ◽  
A Company ◽  
The Web ◽  
Design Construction ◽  
Made In ◽  
Site Types

This report is dedicated to the role of the web site as an important tool for presenting business on the Internet. Classification of site types has been made in terms of their application in the business and the types of structures in their construction. The Models of the Life Cycle for designing business websites are analyzed and are outlined their strengths and weaknesses. The stages in the design, construction, commissioning, and maintenance of a business website are distinguished and the activities and requirements of each stage are specified.

Role of Innate Immune Sensors, TLRs, and NALP3 in Rheumatoid Arthritis and Osteoarthritis

2014 ◽  
Vol 24 (4) ◽  
pp. 243-251 ◽  
Author(s):  
Yuya Takakubo ◽  
G. Barreto ◽  
Yrjo T. Konttinen ◽  
H. Oki ◽  
Michiaki Takagi
Keyword(s):  
Rheumatoid Arthritis ◽  
Innate Immune

Aboutness

2014 ◽  
Author(s):  
Stephen Yablo
Keyword(s):  
Subject Matter ◽  
Philosophy Of Language ◽  
Mental States ◽  
Library Science ◽  
Philosophical Methodology ◽  
Major Advance ◽  
Truth Conditions ◽  
Ways Of Being ◽  
Made In

Aboutness has been studied from any number of angles. Brentano made it the defining feature of the mental. Phenomenologists try to pin down the aboutness features of particular mental states. Materialists sometimes claim to have grounded aboutness in natural regularities. Attempts have even been made, in library science and information theory, to operationalize the notion. However, it has played no real role in philosophical semantics, which is surprising. This is the first book to examine through a philosophical lens the role of subject matter in meaning. A long-standing tradition sees meaning as truth conditions, to be specified by listing the scenarios in which a sentence is true. Nothing is said about the principle of selection—about what in a scenario gets it onto the list. Subject matter is the missing link here. A sentence is true because of how matters stand where its subject matter is concerned. This book maintains that this is not just a feature of subject matter, but its essence. One indicates what a sentence is about by mapping out logical space according to its changing ways of being true or false. The notion of content that results—directed content—is brought to bear on a range of philosophical topics, including ontology, verisimilitude, knowledge, loose talk, assertive content, and philosophical methodology. The book represents a major advance in semantics and the philosophy of language.

Sign in / Sign up

Export Citation Format

Share Document